LeukaemiaLeukaemiass

Leukaemias:Leukaemias: Malignant Disease Malignant Disease of WBC Forming tissue:of WBC Forming tissue:

Lymphoblastic Lymphoblastic (ALL)(ALL)

Acute Acute

Myeloid (AML)Myeloid (AML)

Lymphatic (CLL)Lymphatic (CLL)

Chronic Chronic

Myeloid (CML)Myeloid (CML)

leukaemias:leukaemias: ALL Childhood ALL Childhood AML AML AdultsAdults Acute AcuteAetiology:Aetiology: Unknown in individual Unknown in individual case case

** Viral Viral

** Radiation Radiation

** Chemicals and Drugs Chemicals and Drugs

** Genetics factors Genetics factors

Pathology:Pathology:

BLAST

CELLS

Tissue invasion

(L.N., spleen, liver, skin, C.N.S)

BLOODPancytopenia

+Blastaemia

NormalHaemopoiesis (Depressed)

Bone Marrow

In tumors manifesting as In tumors manifesting as leukemias ,blast accumulating in the leukemias ,blast accumulating in the marrow suppress the growth of marrow suppress the growth of normal hemopoietic cells by physical normal hemopoietic cells by physical displacement and by other poorly displacement and by other poorly understood mechanisms.Eventully understood mechanisms.Eventully this suppresion manifested as bone this suppresion manifested as bone marrow failure. Which account for marrow failure. Which account for the major clinical presentationthe major clinical presentation..

PathogenesisPathogenesisThe principle pathogenic defect in acute The principle pathogenic defect in acute leukemia is a block in differentiationleukemia is a block in differentiation..

This mutation arrest stems from acquired This mutation arrest stems from acquired mutations in specific transcription factors mutations in specific transcription factors that regulate the differentiation of that regulate the differentiation of immature lymphoid or myeloid immature lymphoid or myeloid progenitorsprogenitors..

Normal B cell , T cell,and myeloid Normal B cell , T cell,and myeloid differentiation are regulated by different differentiation are regulated by different lineage -specific transcription factors, lineage -specific transcription factors, accordingly, the mutated transcription accordingly, the mutated transcription factor genes found in acute leukemias factor genes found in acute leukemias derived from each of these lineages also derived from each of these lineages also are distinctare distinct..

Clinical featuresClinical features

--Abrupt,stormy onsentAbrupt,stormy onsent

--Clinical signs and symptoms related to suppressed Clinical signs and symptoms related to suppressed marrow function , including fatigue due to marrow function , including fatigue due to anemiaanemia

--Bone pain and tenderness resulting from marrow Bone pain and tenderness resulting from marrow expansion and infiltration of subperiosteumexpansion and infiltration of subperiosteum..

__Generalized lymphadenopathy, splenomegaly andGeneralized lymphadenopathy, splenomegaly and

Hepatomegaly ,thymic mass in ALLHepatomegaly ,thymic mass in ALL..

--CNS manifestation from meningeal spread. More CNS manifestation from meningeal spread. More common in chidren than adult and ALL than AMLcommon in chidren than adult and ALL than AML..

Blood Picture:Blood Picture: Hb Hb ClinicallyClinically (Normochronic (Normochronic - - - - Pallor, - - - - Pallor, TirednessTiredness Anaemia Anaemia - - - - Dyspnea, etc. - - - - Dyspnea, etc. . . . . =4-9 g/dl)=4-9 g/dl) DIC (AProl) Platelet Count DIC (AProl) Platelet Count - - -- - - Bleeding Bleeding (Thrmbocytopenia(Thrmbocytopenia Tendency Tendency = 10 = 10 –– 80 x 10 80 x 1099/L)/L)

NeutrophilNeutrophil - - - Infections - - - Infections countcount (Fever, (Fever, septicoemia)septicoemia) ( 0.1 ( 0.1 –– 1.5 x 10 1.5 x 1099/L)/L)

Organ infiltration: Organ infiltration: Lymphadenopathy (systemic)Lymphadenopathy (systemic) HepatosplenomegalyHepatosplenomegaly - Gum Hypertrophy in Monocytic - Gum Hypertrophy in Monocytic leukaemialeukaemia (rarely, skin, bone, C.N.S) (rarely, skin, bone, C.N.S)

ViralFungalBacterial

Total WBC count

Normal, low, or increased

Leukaemia:Leukaemia: Neoplastic disease of Neoplastic disease of WBC forming tissue.WBC forming tissue.

Classification (FAB)Classification (FAB)I. Acute lymphoblastic leuk. I. Acute lymphoblastic leuk.

ALLALL Morphological Morphological L1 L1 –– Monomorphic type . . . . Good risk Monomorphic type . . . . Good riskL2 L2 –– Heterogenous type Heterogenous type L 3 L 3 –– Burkitt Burkitt’’s type s type Immunological Immunological 1) Non T, Non B ALL (common)1) Non T, Non B ALL (common) good risk ALLgood risk ALL2) T- ALL2) T- ALL3) B- ALL3) B- ALL

II. Acute Myeloid Leukaemia (AML)II. Acute Myeloid Leukaemia (AML) [ FAB][ FAB]MM00 AML . . . Poorly differentiated AML . . . Poorly differentiated MM11 AML . . . Without Maturation AML . . . Without Maturation MM22 AML . . . With Maturation AML . . . With Maturation MM33 AproL . . . Promyelocytic AproL . . . Promyelocytic MM4 4 AMML . . . MyeloMonocyticAMML . . . MyeloMonocyticMM55 AMOL . . . Monocytic AMOL . . . Monocytic MM66 A. ErythroLeukaemia A. ErythroLeukaemia MM77 A. Megakaryoblastic LA. Megakaryoblastic LAge groups : ALL Age groups : ALL –– mostly in mostly in

children children AML AML –– mostly in mostly in

Adults Adults